Treatment with a nicotine vaccine does not lead to changes in brain activity during smoking cue exposure or a working memory task

AIMS: To assess whether immunization attenuates nicotinic stimulation of the brain and elucidate brain and behavioural responses during exposure to smoking cues and a working memory task. DESIGN: Randomized, placebo-controlled parallel-group, repeated-measures design. SETTING: Maastricht University, the Netherlands. PARTICIPANTS: Forty-eight male smokers were randomized to receive five injections with either 400 mug/ml of the 3'-aminomethylnicotine Pseudomonas aeruginosa r-Exoprotein-conjugated vaccine or placebo. Subjects were tested on two occasions, once after a nicotine challenge and once after a placebo challenge, and were asked to refrain from smoking 10 hours before testing. MEASUREMENTS: Reaction-times and accuracies were recorded during an n-back task. Moreover, regional blood oxygenated level-dependent (BOLD) response was measured during this task and during smoking cue exposure. FINDINGS: Greater activation was found in response to smoking cues compared to neutral cues in bilateral trans-occipital sulcus (P < 0.005); however, this effect did not survive correction for multiple comparisons. There was no difference in brain activity to smoking cues between the treatment groups and no effects of acute nicotine challenge were established. For the n-back task we found working memory load-sensitive increases in brain activity in several frontal and parietal areas (P < 0.0025). However, no effects of immunization or nicotine challenge were observed. CONCLUSION: No significant effects of immunization on brain activity in response to a nicotine challenge were established. Therefore this vaccine is not likely to be an effective aid in smoking cessation.